Pharmaceuticals which enhance serotonergic neurotransmission are useful for the treatment of many psychiatric disorders, including depression and anxiety. The first generation of non-selective serotonin-affecting drugs operated through a variety of physiological functions which endowed them with several side effect liabilities. The more currently prescribed drugs, the selective serotonin reuptake inhibitors (SSRIs), act predominately by inhibiting 5-HT, which is released at the synapses, from being actively removed from the synaptic cleft via a presynaptic serotonin transport carrier.
SSRI's currently available suffers from a serious drawback in that several weeks of treatment is necessary to produce the therapeutic effect. The delayed onset of action is a significant problem, especially in the treatment of patients with severe depression.
It has been shown by Arborelius et. al (Arborelius, L. et al., Naunyn-Schmiedeberg's Arch. Pharmacol. 1995, 352, 157) that acute administration of SSRI's reduces firing of 5-HT neurons of dorsal raphe nucleus in the rodent brain and sustained treatment of SSRI's leads to normalization of the firing activity of the 5-HT neurons. Further more it has been shown by others that the recovery of firing activity of 5-HT neurons is linked to desentization of somatodendritic 5-HT1A autoreceptors. (Invernizzi, R. et al, Eur. J. Pharmacol. 1994, 260, 243.) Hence it has been suggested that simultaneous administration of SSRI's and a 5-HT1A receptor antagonist would lead to rapid onset of antidepressive effect. (Artigas, F. et al, Trends Neurosci. 1996, 19, 378).
Jean-Luc Malleron et. al (Jean-Luc Malleron et. al J. Med. Chem. 1993, 36, 1194) published a series of naphthalenesultam derivatives of formula 1 as selective serotonin uptake inhibitors, but nothing has been mentioned about the 5HT-1A activity. In the same paper the naphthalene sultam was replaced by different heterocycles such as 2 to 7. These compounds were evaluated for serotonin uptake inhibiton.
                Wustrow et al. have disclosed a series of 3-[[4-aryl-1-piperazinyl)alkyl]cyclohexyl]-1H-indoles as dopamine D2 partial agonists in J. Med. Chem. 1997, 40, 250.        
Cipollina et al. have disclosed a series of indolylcycloalkylamines as serotonergic vasoconstrictors for the treatment of vascular or migraine headaches in European Patent Application EP 666258.